A vast number of craniofacial dysmorphologies arise in humans; however, little is known about the normal development of the neurocranium and how these dysmorphologies occur. The research proposed here will broaden the understanding of neurocranial development using the zebrafish as a model system. First, cell-lineage tracing will be used to determine the origins of the neurocranium. This analysis provides a basic tool for understanding neurocranial development and gives inroads to the cellular etiology of dysmorphogenesis. Second, loss- and gain-of-function experiments will be carried out to determine the role of Shh in specifying the anterior cartilages of the neurocranium. Third, cell transplantation experiments will be performed to determine if mutations in Shh effector genes act cell autonomously or non-cell autonomously in development. Last, a forward genetic screen will be used to discover new mutations that affect the development of neurocranial cartilages.